Depressed responsiveness to adrenaline in platelets from apparently normal human donors: a familial trait.
Decreased responsiveness to adrenaline has been observed in five apparently normal unrelated human donors. In four of the donors this trait is inherited. Three of the donors, as well as their affected relatives, also exhibited depressed responsiveness to collagen and vasopressin but normal responsiveness to ADP and thrombin. The other two affected donors exhibit normal responsiveness to most other agonists. Normal responsiveness can be restored in all instances either by incubating the platelet-rich plasma at 20 degrees C or by addition of a low concentration of the divalent cation ionophore, A-23187. All affected platelets which have been examined have ATP and ADP contents, cholesterol to phospholipid ratios, and phospholipid class compositions within the normal range. Both the resting level of cyclic-3'5'-AMP and the ability of adrenaline to prevent elevation of cyclic-3',5'-AMP levels by prostaglandin E1 are normal. Mixing experiments demonstrate the absence of a circulating inhibitor of platelet function and suggest that the defect resides in the platelets. We conclude that the depressed responsiveness of human platelets to adrenaline may result from a defect in Ca2+ mobilization to the cytosol.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001791:Blood Platelet Disorders / Q000097:blood / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D010974:Platelet Aggregation / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D000001:Calcimycin; D000244:Adenosine Diphosphate; D003094:Collagen; D004837:Epinephrine